1. Field of the Invention
The invention relates to delivery systems for local application of topically-active agents to the body, especially for use in the treatment of local pathological or traumatic conditions which are difficult or impossible to treat with systemic medications. In particular, the invention relates to topical delivery systems containing high concentrations of pharmaceuticals or other topically-active agents for both immediate and sustained delivery to the affected body site.
2. Discussion of Related Art
Topical delivery systems for either the sustained or immediate release of topically-active agents are well-known. Of particular relevance are systems based on thermogel carriers, which are liquid at room temperature and gels at body temperature, and consequently promote retention at the treatment site of the pharmaceutical or other agent incorporated in the carrier. Delivery of naked pharmaceuticals (i.e., those merely dissolved or dispersed within the thermogel) is quite rapid, however, despite the occasional characterization of these systems as "sustained release", and these systems accordingly generally employ relatively low concentrations of pharamaceuticals as a therapeutic dosage to avoid excessive delivery.
Also of particular relevance to the invention are known "sustained release" preparations, typically comprising microencapsulated pharmaceuticals. While the pharmaceuticals are generally present in these systems in relatively high concentrations for gradual delivery over time, the systems are generally unsuitable in form for topical use.
The prior art has thus not provided topical delivery systems having a high concentration of topically-active agents which effectively deliver active agents to the treatment site both immediately and over an extended period of time.
Of particular interest herein is the treatment of the oral cavity for gingeval retractions, pits, pockets, and sulci; of the external auditory meatus; of the bony sinuses; of nasal passages and other mucosa-lined body orifices such as the vagina, rectum and urethra; and of punctures, abrasions, burns and other wounds. In the treatment of dental caries, fluoride-containing compositions, such as solutions or gels, are known for use in topical applications, since studies have shown that carie-resistance of tooth enamel increases when fluoride penetrates the enamel from a topical application. Therapeutic treatment of gingevitis often involves very elaborate and somewhat uncomfortable methods of treatment. For example, one known method involves implanting in the periodontal sulcus one or more coils of an antibiotic-impregnated cotton or nylon braided cord. The intent of this temporary implant is to provide a highly sustained localized topical drug delivery; the braided cord is used as a readily shaped device which can serve as a drug reservoir. Application of this implant can cause considerable discomfort to the patient and often multiple implantations are required. As a result, efforts have been directed to more convenient and less uncomfortable methods of treatment of gum disease such as the use of topical medicaments.
Topical medicaments for use in the oral cavity in the treatment of periodontal diseases which may be of relevance to the present invention are described in the following prior art:
Japanese Patent No. 61-418,125 pertains to the use of antibiotics in an ointment base for treating periodontal disease. An antibiotic is mixed with an anhydrous water-soluble ointment base which is applied in the gingival space, where it dissolves allowing rapid release of the antibiotic.
U.S. Pat. No. 4,454,110 is directed to a self-gelling composition for topical application of an active ingredient, for "sustained release" in the oral cavity. The gellable composition comprises a low viscosity, aqueous solution adapted to be converted after mixing and topical application from a liquid solution to a gel state.
U.S. Pat. No. 4,478,822 is directed to a drug delivery system consisting of a thermosetting gel in which an active ingredient is dispersed. This provides for a "prolonged time-release" of a drug from the gelled composition to the site of administration.
U.S. Pat. No. 4,329,333 and U.S. Pat. No. 4,597,959 pertain to a method and to a composition (respectively) in which a multiplicity of microencapsulated liquid droplets containing an active ingredient are applied to the gingival region and thus provide a "slow release" of the micro-encapsulated material into the oral cavity. The microcapsules containing the active ingredients are comprised of cross-linked gelatin materials which dissolve in the mouth and which are dispersed in a paste, cream, or gel.